Suboptimal maternal and cord plasma pyridoxal 5′ phosphate concentrations are uncommon in a cohort of Canadian pregnant women and newborn infants

Abstract

Vitamin B 6 is important in fetal development, but little is known of the vitamin B 6 status of pregnant women and newborns in North America and potential modifying factors. This prospective study determined maternal and cord plasma concentrations of pyridoxal 5′ phosphate (PLP; an indicator of vitamin B 6 status) in a convenience sample of 368 Canadian pregnant women and their newborns. The association of maternal intake of vitamin B 6 and fetal genetic variants with cord plasma PLP and homocysteine concentrations was also examined. Dietary and supplemental intakes of vitamin B 6 were assessed in early and mid to late pregnancy. PLP concentrations were measured in maternal plasma in early pregnancy and at delivery, and in cord plasma. Six fetal variants of the MTHFR and CβS genes were assessed for their association with cord plasma PLP and homocysteine concentrations. Geometric mean (95% CI) PLP concentrations were 107 (98, 116) nmol/L in early pregnancy and 58 (53, 62) nmol/L at delivery, respectively, and 296 (275, 319) nmol/L in cord blood (p < .0001). During early pregnancy and at delivery, 3.6% and 5.5% of women had plasma PLP concentrations <20 nmol/L, respectively. Ninety eight percent of the women with supplemental B 6 intake of at least the recommended dietary allowance had PLP concentrations >20 nmol/L. Fetal genetic variants were not associated with cord PLP and homocysteine concentrations. Vitamin B 6 deficiency is uncommon in a cohort of Canadian pregnant women due largely to prevalent vitamin B 6 supplement use.

Maternal plasma folate concentration is positively associated with serum total cholesterol and low-density lipoprotein across the three trimesters of pregnancy

“…Additionally, maternal folate and total B-12 concentrations declined between the first and second trimesters, whereas PLP concentration dropped across all trimesters. Similar results were found in pregnant Spanish women, in whom plasma folate and total B-12 concentrations decreased from 15 to 24–27 weeks of gestation 27 , and a significant decline in PLP concentration across trimesters was also reported in pregnant Canadian women 28 . Potential mechanisms involved in the decrease of the aforementioned B vitamins by trimester are likely related to increased mother-fetus transport, increased glomerular filtration and hemodilution due to the increment of blood volume during pregnancy 29 – 31 .…”

Supplementation with (6S)-5-methyltetrahydrofolic acid appears as effective as folic acid in maintaining maternal folate status while reducing unmetabolised folic acid in maternal plasma: a randomised trial of pregnant women in Canada

“…Baseline biochemical outcomes are presented in Table 2; outcomes at endline and postpartum visits are presented in Table 3 (erythrocyte folate, serum folate and plasma UMFA) and online Supplementary Table (exploratory outcomes: vitamin B 12 , PLP, total homocysteine, cysteine, methionine, free choline and betaine). While cut-offs during pregnancy are not established, median concentrations of vitamin B 12 and PLP remained above cut-offs for deficiency in non-pregnant women (vitamin B 12 < 148 pmol/l and PLP < 20 nmol/l), and total homocysteine remained < 13 µmol/l (cut-off for hyperhomocysteinaemia) in all participants, at all visits (48,49) . No participants had erythrocyte folate (< 305 nmol/l) or serum folate (< 7 nmol/l) indicative of deficiency at any point (50) .…”

Maternal folic acid and multivitamin supplementation: International clinical evidence with considerations for the prevention of folate-sensitive birth defects

“…2 ) ( Ducker and Rabinowitz, 2017 , Bailey et al, 2015 , O’Leary and Samman, 2010 , Ueland, 2011 , Petersen et al, 20199 , Brosnan et al, 2019 ). Table 5 summarizes one-carbon metabolism cohort studies ( Petersen et al, 20199 , Ray et al, 2002 , Ray et al, 2007 , Visentin et al, 2016 , Visentin et al, 2016 , Fofou-Caillierez et al, 2019 , O’Malley et al, 2018 , Molloy, 2018 , Visentin et al, 2015 , Barzilay et al, 2018 , Plumptre et al, 2018 , Murphy et al, 2021 )

Fig. 2 Focused Diagram of the One-Carbon Metabolism Co-Factors ( Ducker and Rabinowitz, 2017 , Bailey et al, 2015 , O’Leary and Samman, 2010 , Ueland, 2011 ).

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“…Choline intake was less than adequate (<450 mg/d) in 87% of women ( Molloy, 2018 ) PERFORM cohort choline Dietary maternal choline status, not the fetal genotype, influences cord plasma concentrations of choline metabolites ( Visentin et al, 2015 ) PERFORM cohort carbon one elements There were no maternal differences in one-carbon nutrients/metabolites between GDM and control patients. ( Barzilay et al, 2018 ) PERFORM cohort B6 Vitamin B6 deficiency is uncommon, likely due to prevalent vitamin B6 prenatal supplement use ( Plumptre et al, 2018 ) Folic Acid RCT Clinical Trial (FACT) Ancillary Study Folic acid dose (1 or 5 mg) and One Carbon metabolism High dose FA in early pregnancy increases serum folate but not RBC folate concentrations; high dose FA may be supraphysiologic with no evidence of altered 1-carbon metabolism ( Murphy et al, 2021 ) Abbreviations : aOR adjusted odds ratio; B6 vitamin B6; B12 vitamin B12; FA folic acid; NTD neural tube defect; NS non-significant; RBC red blood cell. …”